Our laboratory has documented that thymidine kinase, a key "salvage pathway" enzyme for thymidylate biosynthesis and subsequently DNA replication, has unique properties in human fetal tissue during the period of rapid increase in fetal size and cell mass. The fetal enzyme is exclusively cytoplasmic and is not found in normal adult tissues. On the other hand, fetal thymidine kinase activity reappears in human malignant tumors, cultured tumor cell lines and in human adult fibroblasts transformed with a DNA oncogenic virus. Continuation of this research will be directed toward characterization of fetal thymidine kinase in virus-transformed cells as a host rather than virus-coded enzyme, using enzyme purification and immunologic techniques. We wish to establish that thymidine kinase is one fetal gene function, transmitted vertically in man, repressed in normal post-natal cells and derepressed in cells undergoing carcinogenic change. The study of human thymidine kinase in human virus-transformed cells may also shed light on control of cellular growth in these cells. We have shown that fetal thymidine kinase in normal fetal fibroblasts is significantly stimulated by serum factor(s), whereas thymidine kinase in human adult transformed fibroblasts appears to be functioning at maximal activity and is not responsive to serum growth factors. Evidence to data suggests that virus-transformed cells may produce a factor(s) which stimulates fetal thymidine kinase activity in the transformed cells. This factor(s) must be supplied exogenously to non-transformed cells for cell and maximum thymidine kinase activity. Characterization of these factor(s) will be pursued by standard purification and immunologic procedures. We are also pursuing a collaborative study on karyotypic alterations in cultured lymphoblast lines from individuals with autoimmune disease in tumor lines from mice susceptible to an autoimmune lupus erythematosis-like disease. Our part of this study will be related to identifying the cytogenetic alterations in these various cell lines.